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Cetuximab plus irinotecan administered biweekly with reduced infusion time to heavily pretreated patients with metastatic colorectal cancer and related RAS and BRAF mutation status
Author(s) -
Jensen Benny Vittrup,
Schou Jakob V.,
Yilmaz Mette,
Johannesen Helle H.,
Skougaard Kristin,
Linnemann Dorte,
Hogdall Estrid V.,
Larsen Finn O.,
Johansen Julia S.,
Pfeiffer Per,
Nielsen Dorte L.
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33448
Subject(s) - cetuximab , irinotecan , medicine , colorectal cancer , oncology , cancer
Metastatic colorectal cancer (mCRC) is treated with cetuximab 250 mg/m 2 administered weekly over 1 hour or biweekly (q2w) over 3.5 hours when combined with irinotecan. This prospective study investigated cetuximab 500 mg/m 2 plus irinotecan 180 mg/m 2 administered q2w over 1.5 hours independent of RAS or BRAF mutation status in mCRC patients in a third‐line setting. The intention‐to‐treat population included 181 patients. No patients had complete response, 18% had partial responses (PR) and 48% stable disease (SD). For cetuximab, a relative dose intensity of ≥90% was reached in 78% and for irinotecan in 67% of the patients. Grade 3 to 4 toxicities were pain (17%), fatigue (9%), neutropenia (8%), diarrhea (8%), rash (8%), infection (7%) and hypersensitivity (3%). No deaths occurred. Next‐generation sequencing in 96.7% of the patients revealed that 50.3% had RAS and BRAF V600E wild type (WT), with a mutation type (MT) in 45.1% of the RAS and 4.4% of the BRAF V600E genes. In patients with RAS‐ WT and RAS‐ MT tumors, a PR was obtained in 32% and 4% ( P = .3) and an SD in 43% and 53%, respectively, with a superior PFS (6.2 vs 3.7 months; hazard ratio [HR] 2.12, P = .00001) and OS (12.9 vs 8.8 months; HR 1.71, P = .0008). Treatment efficacy was poor in 7.4% of patients with an RAS mutation outside KRAS exon 2 and in 38% of patients with KRAS exon 2 mutations. Administration of cetuximab and irinotecan q2w, shortening treatment time from 3.5 to 1.5 hours, is recommended as standard therapy.